Fused quinazolinones

ABSTRACT

Fused quinazolinone derivatives of the formula,   WHEREIN R1 and R2 are individually hydrogen, C1 4 alkyl, C1 4 alkoxy, nitro, C1 4 alkylsulfonyl or halogen; R3 is pyridyl, thienyl or a group of the formula   WHEREIN R4 is hydrogen or halogen; R is hydrogen, C1 4 alkyl, C2 5 alkenyl, aralkyl, (C3 6 cycloalkyl)C1 4 alkyl, (C1 4 alkoxy)C1 4 alkyl, (C1 4 alkylthio)C1 4 alkyl, hydroxy-C1 4 alkyl or C2 5 alkanoyloxy-C1 4 alkyl; Y is oxygen, or a group of the formula N - R5, wherein R5 is hydrogen or C1 4 alkyl; and Z is C2 5 alkylene or alkenylene, are prepared by contacting a trihaloacetamidophenyl ketone derivative of the formula,   WHEREIN R1, R2, R3 and R are as defined above; and X1, X2 and X3 are halogen, with an amine of the formula, HY - Z - NH2, wherein Y and Z are as defined above, or a salt thereof, in the presence of a solvent or a mixture thereof. They have remarkable pharmacological properties such as anti-inflammatory, analgesic and/or uricosuric activities.

United States Patent n91 Inaba et al.

[ FUSED QUINAZOLINONES [75] Inventors: Shigeho lnaba, Takarazuka;

Michihiro Yamamoto, Toyonaka; Kikuo lshizumi lkeda; Kazuo Mori. Kobe;Masao Koshiba, Takarazuka; Hisao Yamamoto, Nishinomiya. all of Japan[73] Assignee: Sumitomo Chemical Co., Ltd..

Osaka, Japan [22] Filed: July 23, 1973 [2l] Appl. No: 381,571

Related US. Application Data [63] Continuation-impart of Scr. N0.l72.562. Aug. l7.

197 l abandoned.

[52] US. Cl. 260/244 R; 260/25l A; 260/2564 F; 260/2565 R; 260/295 AM;260/3322 R;

[5] Int. Cl C07d 87/20 [58] Field of Search 260/244, 25L 256.4. 256.5

{56] References Cited OTHER PUBLICATIONS Sato et al. Yakugaku Zasshi.Vol. 90, pp. 629-633 1970).

Primary E.runiine)-Harry l. Moat: Almmey. Agent, or FirmStevens, Davis,Miller & Mosher I57] ABSTRACT Fused quinazolinone derivatives of theformula,

wherein R and R are individually hydrogen, C, ulkyl, C alkoxy nitro, Calkylsulfonyl or halogen; R is pyridyl. thienyl or a group of theformula wherein R is hydrogen or halogen; R is hydrogen. C, alkyl, Calkenyl, aralkyl. (C cyeloall yl)C alkyl. (C, alkoxy)C, alkyl (C,,alkylthio)C, alkyl hydroxy-C alkyl or C alkanoyloxy-C alkyl; Y isoxygen, or a group of the formula N R wherein R is hydrogen or C, alkyl;and Z is C alkylene or alkenylene. are prepared by contacting atrihaloacetamidophenyl ketone derivative of the formula,

1 R N c0 04L 1 R wherein R, R R and R are as defined above; and X,, Xand X are halogen. with an amine of the formula. HY Z NH wherein Y and Zare as de fined above, or a salt thereof, in the presence of a solventor a mixture thereof, They have remarkable pharmacological propertiessuch as anti-inflammatory. analgesic and/or uricosuric activities.

21 Claims, No Drawings FUSED QUINAZOLINONES CROSS REFERENCE TO THERELATED APPLICATION This application is a continuation-in-part ofapplication Ser. No. l72.562 filed Aug. 17, 197], now abandoncd.

This invention relates to novel quinazolinone derivatives and a novelprocess for production thereof.

More particularly, the present invention relates to fused quinazolinonederivatives of the formula.

wherein R and R are individually a hydrogen atom, a C alkyl group, a Calkoxy group, a nitro group, a C alkylsulfonyl group or a halogen atom;R is a group of the formula (wherein R is a hydrogen atom or a halogenatom), a pyridyl group or a thienyl group; R is a hydrogen atom, a Calkyl group, a C alkenyl group, an aralkyl group, a C cyeloalkyl-C alkylgroup. a C alkoxy- C, alkyl group, a C alkylthio-C alkyl group, ahydroxy-C alkyl group or a C alkanoyloxy-C alkyl group; Y is an oxygenatom or a group of the formula N R (wherein R:, is a hydrogen atom or aC alkyl group); and Z is a C alkylene or alkenylene group, which maycontain among the carbon chain one oxygen atom, and may be optionallysubstituted by one or two C alkyl groups, and further, the two alkylgroups on adjacent carbon atoms of the alkylene or alkenylene group maybe joined to form a benzene ring, and a process for production andpharmaceutical use of the same.

In the compounds of the formula (I), the term "alkyl" means bothstraight and branched chain aliphatic hydrocarbon radicals, and the Calkyl group includes. for example. methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl and tertiary-butyl groups; the aralkyl group includes,for example, benzyl, phenethyl, methoxy benzyl, chlorobenzyl andfluorobenzyl groups; the C alkoxy group includes, for example, methoxy,ethoxy, n-propoxy, isopropoxy, n-hutoxy and tertiarybutoxy groups; the Calkylthio group includes, for example, methylthio, cthylthio andisopropylthio groups, the C alkanoyloxy group includes, for example,acetoxy, propionyloxy and isobutyryloxy groups; the C alkcnyl groupincludes, for example, vinyl, allyl, methallyl, butenyl and crotylgroups; and the C cycloalkyl group includes, for example, cyclopropyl,cyclobutyl, cyclopcntyl and cyclohexyl groups.

The quinazolinone derivatives of the formula (I), which include novelcompounds, have remarkable pharmacological properties, such asauntiinflammatory, analgesic and/or uricosurie activities.

Particularly, the present inventors have found that novel quinazolinonederivatives of the formula,

R R O (I a) N G wherein R,, R R and Z are as defined above; and R hasthe same definition as that of R defined above except that R can not bea hydrogen atom, possess much more excellent anti-inflammatory and/oruricosuric effects in animal tests with low toxicity. lllustratively, 9-chloro-2.3,6, l Ob-tetrahydro-fi-methyll0b-phenyl-5 H-oxazolol3,2-C]-quinazolin-5-one shows remarkable inhibitory action forcarrageenin-induced edema in rat, while no toxic symptoms are observedand occult bleeding is negative in feces after oral administration of2,000 mg/kg in rat. The anti-inflammatory activity of the presentcompound is more effective than that of l2-diphenyl-3,5-dioxo-4-(n-butyl)-pyrozolidine (phenylbutazone), and theacute, subacute and chronic toxicities of the present compound are muchlower than those of phenylbutazone. Moreover, this compound possessesmore marked uricosuric activity than the known drugs such asp-(dipropylsulfamoyl)benzoic acid (probenecid).

Thus, an object of the present invention is to provide a novel anduseful process for producing commercially such valuable compounds.Another object of the present invention is to provide novelquinazolinone derivatives of the formula (l-a) excellent inanti-inflammatory and/or uricosuric effects. Other object of the presentinvention is to provide a pharmaceutically acceptable compositioncontaining one or more quinazolinone derivatives of the formula (La),and a pharmaceutically acceptable diluent or carrier. Further objects ofthe present invention will be apparent from the accompanying disclosureand discussion.

In order to accomplish these objects, the present invention provides aprocess for producing quinazolinone derivatives of the formula (I),which comprises contacting a trihaloacetamidophenyl ketone derivative ofthe formula,

R R3 2 I 1 (11) N coc x 1 x R 3 wherein R R R and R are the same asdefined above; and X,, X and X are same or different halogen atoms, withan amine of the formula,

HY 2 NH (lll) wherein Y and Z are the same as defined above. or a saltthereof.

A trihaloacetamidophenyl ketone derivative of the formula (ll) can, forexample. be prepared by contacting a corresponding Z-aminophenyl kctonederivative of the formula,

c (IV) NH R wherein R R R and R are the same defined above, with atrihaloacetic acid or a reactive derivative thereof.

In preparing a quinazolinone derivative of the for' mula (l) accordingto the process of the present invention, a trihaloacetamidophenyl ketonederivative of the formula (ll) is reacted with an amine of the formula(lll) or a salt thereof, preferably in the presence of a solvent orsolvent mixture.

Suitable solvents are, for example, methanol, ethanol, isopropanol,tertiary-butanol, Cellosolve, pyridine, dimethyl sulfoxide anddimethylformamide. Excess of the amine of the formula (lll) may be alsoused as a solvent.

When a salt of the amine of the formula (lll) is employed, it isdesirable to carry out the reaction in the presence of a base, which mayinclude an inorganic base such as sodium hydroxide, potassium hydroxide,sodium carbonate or potassium carbonate, or an organic base such aspyridine, triethylamine, tri-npropylamine or dimethylaniline.

Generally, the reaction may proceed at room temperature, but higher orlower temperatures may be employed satisfactorily.

A quinazolinone derivative of the formula,

R 0 2 3 Y x N (I-b) s H 0 1 wherein R R R and Z are the same as definedabove; and Y has the same definition as that of Y defined above exceptthat Y' can not be a group of the formula NH, which is obtainedaccording to the abovementioned process may be further converted to acorresponding N-substituted quinazolinone derivative of the formula,

wherein R R R;,. Y and Z are the same as defined above; and R has thesame definition as that of R defined above except that R cannot be ahydrogen atom. by reaction with a reactive derivative of the compound ofthe formula,

wherein R is the same as defined above.

As the reactive derivative, there may be preferably employed a halidesuch as chloride, bromide or iodide; a sulfonate such asp-toluenesulfonate or trichloromethanesulfonate; or a sulfate such asdimcthyl sulfate or diethyl sulfate.

The reaction can be carried out by treating a quinazolinone derivativeof the formula (l-b) with a reactive derivative of the compound of theformula (V) in the presence of a base, or alternatively by treating thequinazolinone derivative with a base to obtain a basic metal saltthereof and then treating the resulting metal salt with the reactivederivative of the formula (V).

Preferable bases in above reaction include, for example, alkali metalhydrides such as sodium hydride or potassium hydride; alkali metalamides such as sodium amide or potassium amide; organolithium compoundssuch as butyl lithium or phenyl lithium; and alkali metal alkoxides suchas sodium methoxide, potassium methoxide, sodium ethoxide, potassiumcthoxide or potassium tertiary-butoxide.

The reaction is preferably effected in an organic solvent or solventmixture. The suitable solvents include, for example, benzene, toluene,xylene, dimethylformamide, dimethylaeetamide, ether, tetrahydrofuran,diglyme, acetone and dimethylsulfoxide, and a mixture thereof.

The reaction is generally effected at a temperature within a range offrom about room temperature to the boiling point of the solventemployed.

According to the process of the present invention, there are obtained,for example, the following quinazolinone derivatives:

1,2,3, l Ob-Tetrahydrol Ob-phenyl-imidazol l ,2-C]

quinazolin-5( 6H )-one Q-FIuoro-l ,2,3,10b-tetrahydro- IOb-phenyI-imidazo- [l,2-Clquinazolin-5(6H)-one 9-Chlorol ,2,3,lOb-tetrahydrol Ob-phenylimidazol l ,2-C ]quinazolin-5(6H )-one 9-Bromol,2,3, 1 Ob-tetrahydrol0b-phenylimidazol 1 ,2-C ]quinazolin-5 6H )-one8-Chlorol ,2,3, l 0btetrahydrol Ob-phenylimidazo[I,2-Clquinazolin-5(6H)-one 7-Chlorol ,2,3, Ob-tetrahydrolOb-phenylimida7.o[ l,2-C]quinazolin-5( 6H)one 7,9-Dichloro-l ,2,3, lOb-tetrahydrolOb-phenylimidazo[ l,2-C|quinazolin-5(6H)-one 9-Methyll,2,3, l Ob-tetrahydrol Ob-phenylimidazol 1,2-C ]quinazolin-5 6H )-one9-Nitrol ,2,3, l Ob-tetrahydro- IOb-phenylimidazo[ l ,2-Clquinazolin-S(6H l-one The present invention is further explainedreffering to the following examples of more preferred embodimcntsthereof, which are presented for the purpose of illustration and are notintended to limit the scope of the invention.

EXAMPLE 1 To a solution of 3.77g of 2-trichloroacetamido-5-ehlorobenzophenone in 70 ml of ethanol was added ml of ethylenediamine,and the resultant mixture was heated under reflux for 2 hours. Aftercooling with ice, the resulting crystals were separated by filtration,washed with water and dried to give 2.12 g of 9-chloro-1,2,3,10b-tetrahydro-lOb-phenyl-imidazol1,2- Clquinazolin-5(6H)-one.Recrystallization from ethanol-dimethyl-formamide gave colorlessneedles. having a melting point of 274 275C.

EXAMPLE 2 To a solution of 1.89 g of 2-trichloroaeetamido-5-chlorobenzophenone in 50 ml of ethanol was added 2.22 g of1,3-diaminopropane, and the resultant mixture was allowed to stand atroom temperature overnight. Then, the reaction mixture was poured into300 ml of water, and the precipitate thus formed was separated byfiltration, washed with ether and dried to give 1.25 g of-ehloro-1,2,3,4,7,1 lb-hexahydro-l1hpheny1-6H-pyrimido[1,2-C]quinazolin-6-one, having a melting point of275 276C.

EXAMPLE 3 Using a procedure similar to that described in Example 1, butreplacing ethylenediamine by N methylethylenediamine, there was obtained9-chloro- 1,2,3,10b-tetrahydro-l-methyl-lObphenylimidazo[1,2-C]quinazolin-5(6H)-one, having a melting point of 270 271C.

EXAMPLE 4 To a solution of 1.89 g of 2-trichloroacetamido-5-chlorobenzophenone in 40 ml of dimethylsulfoxide was added 3.05 g ofmonoethanolamine, and the resultant mixture was heated at about 90C for3 hours. After cooling, the reaction mixture was poured into 300 ml ofwater and extracted with chloroform. The extract was washed twice withwater and dried over anhydrous sodium sulfate. The solvent was removedunder reduced pressure. The residue was chromatographed on silica gelusing chloroform as an eluent to give 1.0 g of 9-chloro-2,3,6, lOb-tetrahydro- 1 Ob-phenyl-SH- oxazolo[ 3 ,Z-CIquinaZoIin-S-one.Recrystallization from ethanol gave pale yellow prisms, having a meltingpoint of 219 220C.

EXAMPLE 5 To a solution of 3.77 g of 2-trichloroacetamido-5-ehlorobenzophenone in 100 ml of ethanol was added 3.05 g ofmonoethanolamine. and the resulting mixture was refluxed for 2 hours.Then, the solvent was removed under reduced pressure. The residue waschromatographed on silica gel using chloroform as an cluent to give 2.25g of 9-chloro-2,3,6,10b tetrahydro- 10b-phenyl-5H-oxazolo[3,2-Clquinazolin-5-one, having a melting point of 216 217C.

EXAMPLE 6 Using a procedure similar to that described in Example 5, butreplacing 2-trichloroacetamido-S- chlorohenzophenone by 2-(N-methyltrichloroacetamido)-5 chlorobenzophenone. there was obtained9-chloro-2,3,6.1(lh-tetrahydro-6-mcthyl-10bphenyl-SH-oxazolo[3.2-C]quinazolin-5'one. having a metling point of 124 125C.

EXAMPLE 7 To a solution of 1.27 g of 2-triehloroacetamido-S bromophenyl2-pyridyl ketone in 20ml ofdimcthylsulfoxide was added 1.83 g ofmonoethanolamine. and the resultant mixture was heated in an oil bath atC (bath temperature) for 3 hours. After cooling, the reaction mixturewas poured into 100 ml of water and the resulting mixture was extractedwith dichloromcthane. The extract was washed with water and dried overanhydrous sodium sulfate. The solvent was removed under reducedpressure. The residue was chromatographed on silica gel using chloroformas an eluent to give 0.6 g of 9-bromo-2,3,6,lllh-tetrahydro-l0b-(2-pyridyl)-5H-oxazolol3,2-Clquinazolin-S-one, having a melting point of241 242C.

EXAMPLE 8 To a solution of 3.77 g of 2-trichloroacetamido-S-chlorobenzophenone in 50 ml ofdimethylsulfoxide was added 5.26 g of242-hydroxyethoxy)ethylamine, and the mixture was heated at C for 3hours. After cooling, the reaction mixture was poured into 300 m1 ofwater and the resulting mixture was extracted with chloroform. Theextract was washed with water and dried over anhydrous sodium sulfate.The solvent was removed under reduced pressure. The residue wasehromatographed on silica gel using ethyl acetate as an eluent to give2.4 g of a colorless oil, which was crystallized from petroleumbenzin-ethanol to yield 12 chloro-2,3,5,6,9,l 3b-hexahydro- 13b-phenyl-8H [l.6,3,]dioxazocinol3,2-C]quinazolin-8-one, having amelting point of 212 214C.

EXAMPLE 9 To a solution of 1.89 g of 2-trichloroacetamido-5-chlorobenzophenone in 40 ml of dimethylsulfoxide was added 3.25 g ofo-phenylenediamine, and the resultant mixture was heated at 100C for 13hours. After cooling, the reaction mixture was poured into 200 ml ofwater and the precipitates were separated by filtration, washedsuccessively with water and ether, and dried to give 0.86 g of lightbrown crystals, which were recrystallized from acetone-dimethylformamideto yield colorless fine needles of l 1-chloro-1,12b-dihydro-l2-phenyl-benzimidazol1.2-C]quinazolin-7(8H)-one, having a melting point ofabove 300C.

EXAMPLE 10 To a solution of 1.5 g of 9-chloro-2,3.6 l 0btetrahydro- 1Ob-phenyl-SH-oxazolol 3 ,2-C1quinaz0lin- 5-one in 20 ml ofdimethylformamide was added 0.21 g of 62.5 percent sodium hydride. Theresultant mixture was stirred with heating at 50 55C for 1 hour, and1.42 g of methyl iodide was added thereto at room temperature. Then, themixture was heated at 55 60C for 3 hours. After cooling, the reactionmixture was poured into 100 ml of water and acidified with hydrochloricacid. The resulting mixture was extracted with 50 m1 of chloroform andthe chloroform layer was washed successively with dilute hydrochloricacid and water. and dried over anhydrous sodium sulfate. The solvent wasremoved under reduced pressure. The residue was chromatographed onsilica gel using chloroform as an eluent to give 1.2 g of9-chloro-2,3,6,10btetrahydro-b-methyl-1()h-phenyLSH-oxazolo[3,2Clquinazolin-S-one, having a melting point of 124 125C.Recrystallization from ethanol gave colorless prisms, having a meltingpoint of 136 137C.

EXAMPLE 1 1 To a solution of 3.61 g of9-chloro-2,3,6,l()btetrahydro-lb-phenyl-5H-oxazolol3,2-Clquinazolin-5-one in 80 ml of dimethylformamide was added 0.50 g of 64 percentsodium hydride. The resultant mixture was stirred with heating at 100Cfor 30 minutes and 2.3 g of 90 percent cyclopropylmethyl bromide wasadded thereto at room temperature. Then, the mixture was heated at 100Cfor 5 hours. After cooling, the reaction mixture was poured into 400 mlof water. The resulting mixture was extracted with chloroform and thechloroform layer was washed twice with dilute hydrochloric acid. anddried over anhydrous sodium sulfate. The solvent was removed underreduced pressure. The residue was crystallized from ethanol to give 3.05g of colorless prisms of 9-chloro-2,3,6, IOb-tetrahydro-6-cyclopropylmethyl-10b-phenyl-5H-oxazolo[3,2- C]quinazolin-5-one,having a melting point of 143 EXAMPLE 12 To a solution of 7.75 g of2-trichloroacetamido-S nitrobenzophenone in 50 ml. of dimethylsulfoxidewas added 1.47 g of monoethanolamine, and the mixture was heated at 100Cfor 2 hours. After cooling, the reaction mixture was poured into 500 ml.of water and the resulting precipitate was collected by filtration,washed successively with water and ether to give 3.52 g of9-nitro-2.3,6,l0b-tetrahydro-IOb-phenyl-SH-oxazolol3,2-C]quinazolin-5-one, having a melting point of 275 276CEXAMPLE 13 Using a procedure similar to that described in Example 12,but replacing 2-trichloroacetamido-5- nitrobenzophenone by2-trichloroacetamido-5- chlorophenyl 2-thienyl ketone, there wasobtained 9- chloro-2,3,6,l0b-tetrahydro-10b-( 2-thienyl)-5H-oxazolol3,2-Clquinazolin-5 one, having a melting point of 193 194C.

EXAMPLE 14 To a solution of 0.93 g of9-nitro-2,3,6,l0btetrahydrob-phenyl-5 H-oxazolo[ 3 ,2-C ]quinazo1in-5-one in 10 ml. of dimethylformamide was added 0.18 g of 52.9 percentsodium hydride. The mixture was stirred with heating at 60C for 1 hr.then, 0.68 g of henzyl bromide was added thereto. The resulting mixturewas heated at 100C for 4 hours. After cooling, the reaction mixture waspoured into 50 ml. of water and the resulting precipitates werecollected by filtration. washed with water and dried. The crude productwas recrystallized from a mixture of methanol and carbon tetrachlorideto give 1.0 of 9-nitro-2,3,6,10btetrahydro-(J-benzyllOb-phenyl-5H-oxazolol 3,2- C]quinazolin-S-one as yellowish brown prisms,having a melting point of 96 98C (decomp).

EXAMPLE 15 Using a procedure similar to that described in Example 14,but replacing benzyl bromide by methyl iodide. there was obtained9-nitro-2.3,6,l0b-tetrahydro-6-methyl-lUb-phenyl-SH-oxazolol3,2-Clquinazolin- 5-one as pale yellowscales. having a melting point of 135.5 136.5C.

EXAMPLE 16 Using a procedure similar to that described in Example 14,but replacing benzyl bromide by 2- isopropoxyethyl chloride, there wasobtained 9-nitro-2,3,6,10b-tetrahydro-6-(2-isopropoxyethyll-10bpheny1-5Hoxazolo[3,2-C]quinazolin-5-one as yellow scales having a melting point of 123124C.

EXAMPLE 17 Using a procedure similar to that described in Example 11,but replacing cyclopropylmethyl bromide by 2-methylthioethyl chloride,there was obtained 9- chloro-2,3,6,10btetrahydro-6-(2-methylthiocthyl)-IOb-phenyl-SH-oxazolol 3,2C lquinazolin-S -one as colorless needles,having a melting point of 145 146C.

EXAMPLE 18 Using a procedure similar to that described in Example 1 1,but replacing cyclopropylmethyl bromide by 2- acetoxyethyl chloride,there was obtained 9-chloro-2,3,6,10b-tetrahydro-6-(2'acetoxyethyl)-10b-phenyl- SH-oxazolo[3,2-Clquinazolin-5-one as colorless prisms, having a melting point of121 123C.

EXAMPLE 19 To a suspension of 1 1.3 g of 2-trichloroacetamido-5-chlorobenzophenone in m1. of ethanol was added 4.51 g of3-amino-l-propanol. The mixture was heated under reflux for 3 hours.Then, 1.7 g of potassium hydroxide was added thereto and the resultingmixture was further refluxed for 3 hours. After cooling, the precipitatewas filtered off and washed with ethanol. The filtrate was concentratedunder reduced pressure and to the residue was added 200 ml. of water.The resulting solid was collected by filtration, washed with water anddried to give 9.87 g of 10-chloro-3,4,7,l 1btetrahydro-llb-phenyl-2H,6H-l l ,3 ]oxazino[3,2- Clquinazolin--one.Recrystallization from ethanol gave pale yellow prisms, having a meltingpoint of 202 203.5C.

EXAMPLE 20 Using a procedure similar to that described in Example 19,there was obtained2,3,6,IOb-tetrahydro-lObphenyl-5H-oxazolo[3,2-Clquinazolin-S-one ascolorless fine crystals, having a melting point of 193.5 194.5C.

EXAMPLE 21

1. A QUINAZOLINONE DERIVATIVE OF THE FORMULA, 2.2,3,6,10b-Tetrahydro-6-methyl-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one.3. 9-Chloro-2,3,6,10b-tetrahydro-6-methyl-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one. 4.6,9-Dimethyl-2,3,6,10b-tetrahydro-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one. 5.9-Nitro-2,3,6,10b-tetrahydro-6-methyl-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one.6.9-Chloro-2,3,6,10b-tetrahydro-6-cyclopropylmethyl-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one. 7.9-Nitro-2,3,6,10b-tetrahydro-6-benzyl-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one.8.9-Nitro-2,3,6,10b-tetrahydro-6-(2-isopropoxyethyl)-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one.9. 9-Chloro-2,3,6,10b-tetrahydro-6-(2-methylthioethyl)-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one. 10.9-Chloro-2,3,6,10b-tetrahydro-6-(2-acetoxyethyl)-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one. 11.9-Chloro-2,3,6,10b-tetrahydro-6-(2-hydroxyethyl)-10b-phenyl-5H-oxazolo(3,2-C)quinazolin-5-one. 12.9-Chloro-2,3,6,10b-tetrahydro-6-methyl-10b-(2-thienyl)-5H-oxazolo(3,2-C)quinazolin-5-one. 13.10-Chloro-3,4,7,11b-tetrahydro-7-methyl-11b-phenyl-2H,6H-(1,3)oxazino(3,2-C)quinazolin-6-one. 14.10-Methoxy-3,4,7,11b-tetrahydro-7-methyl-11b-phenyl-2H,6H-(1,3)oxazino(3,2-C)qunazolin-6-one. 15.10-Methylsulfonyl-3,4,7,11b-tetrahydro-7-methyl-11b-phenyl-2H,6H-(1,3)oxazino(3,2-C)quinazolin-6-one. 16.10-Chloro-3,4,7,11b-tetrahydro-7-methyl-11b-(o-fluorophenyl)-2H,6H-(1,3)oxazino(3,2-C)quinazolin-6-one. 17.10-Nitro-3,4,7,11b-tetrahydro-7-methyl-11b-phenyl-2H,6H-(1,3)oxazino(3,2-C)quinazolin-6-one. 18.10-Chloro-3,4,7,11b-tetrahydro-7-allyl-11b-phenyl-2H,6H-(1,3)oxazino(3,2-C)quinazolin-6-one. 19.10-Chloro-3,4,7,11b-tetrahydro-7-methoxymethyl-11b-phenyl-2H,6H-(1,3)oxazino(3,2-C)quinazolin-6-one. 20.10-Nitro-3,4,7,11b-tetrahydro-7-(2-acetoxyethyl)-11b-phenyl-2H,6H-(1,3)oxazino(3,2-C)quinazolin-6-one. 21.10-Chloro-3,4,7,11b-tetrahydro-7-methyl-11b-(2-pyridyl)-2H,6H-(1,3)oxazino(3,2-C)quinazolin-6-one.